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Biomedical subjects

D R Waud

Publications and source records attributed to D R Waud.

At least 37 records · Page 2Linked to original sources
PubMed1981

Temperature and potency of d-tubocurarine and pancuronium in vitro.

The concentrations of d-tubocurarine and pancuronium producing 50% block of the indirectly elicited twitch were determined in isolated mouse nerve-diaphragm preparations at 37 and 25 C. The contralateral side was used as a control in a 2 x 2 factorial analysis of variance. Cooling shifted the dose-response curves for both drugs to the left, but only slightly (from 1.69 +/- 0.022 microM to 1.49 +/- 0.021 microM with d-tubocurarine and from 0.65 +/- 0.012 microM to 0.46 +/- 0.009 microM with pancuronium). The dose-response relationship was, however, so steep (Hill coefficient approximately 5 to 6) that a slight horizontal shift of the dose-response curve corresponds to a considerable decrease in the twitch response at a concentration midway between the curves. Thus, studies using only the concentration that produces partial block of twitch responses misleadingly suggest a large effect of temperature. Similarly, if in another system the curve were to shift to the right even only slightly, a temperature effect in the reverse direction might be reported. It is concluded that temperature appears to have little influence on cellular potency of neuromuscular blocking agents.

Animals↗
PubMed1980

Effects of non-depolarizing neuromuscular blocking agents on the cardiac vagus nerve in the guineapig.

The ability of gallamine, metocurine, pancuronium, tubocurarine and atropine to block the response to postganglionic stimulation of the vagus nerve were measured in isolated, spontaneously beating guineapig atria. From analysis of the results in conjunction with those of earlier assays of concentrations that block effects of preganglionic vagal stimulation, it was concluded that only tubocurarine possessed ganglionic blocking activity. From calculation of the extent of block of muscarinic receptors at drug concentrations which blocked the response to postganglionic vagal stimulation, it was concluded that gallamine and pancuronium have an antivagal action exerted most probably on the postganglionic nerve terminal, and that this action is the most likely explanation of the tachycardia seen clinically with these two drugs.

Animals↗
PubMed1980

Interaction of calcium and potassium with neuromuscular blocking agents.

Dose-response curves for blockade of the indirectly elicited twitch of isolated guineapig nerve-lumbrical muscle preparations were determined for tubocurarine and pancuronium in the presence of potassium 2,4 and 6 mmol litre-1 and calcium 1,2 and 3 mmol litre-1. Increases in concentration of either ion decreased the sensitivity of the preparation to both drugs. Over the physiological range of concentrations of potassium and calcium, 36% and 27% variation in dosage can be expected.

Animals↗
PubMed1979

Effects of volatile anesthetics on directly and indirectly stimulated skeletal muscle.

Isolated guinea pig nerve-lumbrical muscle preparations were exposed to halothane, methoxyflurane, isoflurane, enflurane, fluroxene, and diethyl ether. The temporal courses of the effects on indirectly and directly elicited twitch responses were determined over a range of concentrations for each agent. When the anesthetics were compared at concentrations equivalent in terms of minimum alveolar concentration (MAC), a spectrum was observed in which halothane, methoxyflurane and isoflurane depressed the indirect twitch response at 3.5--5 MAC and the direct twitch response at 8--10 MAC. Diethyl ether and fluroxene depressed the indirect twitch response at 2--3.5 MAC and the direct twitch response at 3--6 MAC. Enflurane depressed the indirect response at 1.5--2.5 MAC and the direct response at 6--8 MAC. When the anesthetics were compared at concentrations equivalent in terms of their abilities to depress end-plate depolarization, however, all anesthetics were equipotent. Depression of the indirect twitch response occurred only when anesthetic concentrations were great enough to depress depolarization by 50 per cent.

Anesthetics↗
PubMed1978

The role of uptake of noradrenaline of its positive inotropic effect in relation to muscle geometry. Statistical evaluation.

1. The influence of saturable drug uptake on the drug concentration near the receptor sites was shown theoretically to depend on the geometry of the preparation; increases in the volume/surface ratio (V/S) of the preparation decrease the sensitivity of the preparation to an agonist inactivated in the tissue. 2. The positive inotropic effect of (-)-noradrenaline was found to depend on the ratio V/S of the preparation; papillary muscles with larger V/S were less sensitive to the drug and showed steeper noradrenaline concentration-effect curves. 3. An algorithm for the statistical estimation of the parameters of the saturable uptake process was derived. It was applied to the positive inotropic noradrenaline effect in relation to muscle geometry. As an analysis of variance showed, the model explained a significant proportion of the shift of (-)-noradrenaline concentration-effect curves associated with variation in size of the preparation.

Animals↗
PubMed1978

A vagolytic action of neuromuscular blocking agents at the pacemaker of the isolated guinea pig atrium.

To examine the basis of tachycardia seen clinically with some neuromuscular blocking agents, the potencies of d-tubocurarine, dimethyltubocurarine, gallamine, and pancuronium in antagonizing the effects of vagal stimulation on the guinea pig atrial pacemaker were determined and expressed as an ED50 for vagal blockade. These ED50 values were compared with the respective potency values of these agents at the motor endplate. This comparison showed that in clinical doses, gallamine and pancuronium may reach levels that produce vagal blockade. Comparison with atropine indicated that the vagolytic action of the neuromuscular blocking agents was not attributable to receptor occlusion, but reflected instead an action on the vagus nerve itself.

Animals↗
PubMed1975

The effects of diethyl ether, enflurane, and isoflurane at the neuromuscular junction.

The actions of diethyl ether, enflurane, and isoflurane at the neuromuscular junction were examined in isolated guinea pig lumbrical muscles. These anesthetics depressed the ability of carbachol to depolarize the endplate region; this depression of depolarization did not show competitive kinetics. None of the anesthetics altered the affinity of the acetylcholine receptor for d-tubocurarine, i.e., the dissociation constant of d-tubocurarine was unchanged. Since diethyl ether, enflurane, and isoflurane produced no observable alteration of the receptor, the antagonism of the drug-induced depolarization of the neuromuscular junction appears to be exerted at a stage subsequent to reaction with the receptor. (Key words: Anesthetics, volatile, diethyl ethers; Anesthetics, volatile, euflurane; Anesthetics, volatile, isoflurane; Neuromuscular relaxants, d-tubocurarine; Neuromuscular junction.).

Acetylcholine↗
PubMed1975

Depolarization block and phase II block at the neuromuscular junction.

The effects of repeated doses of decamethonium or succinylcholine in muscles of the cat, dog, and rabbit have been examined. In particular, the relation of degree of neuromuscular block to intensity of the electrical change at the end-plate region has been found to be more consistent when the peak spatial gradient of depolarization is used as a measure of electrical effect than when the peak depolarization is used; the reason for this difference is discussed. A plot of twitch height against electrical change provides a convenient frame of reference for following the development of phase II block quantiatively. Examples presented show that the extent and kinetics of phase II block can vary considerably among species or among muscles in a given species.

Anesthesia, Intravenous↗
PubMed1975

In vitro measurement of margin of safety of neuromuscular transmission.

The margin of safety of neuromuscular transmission was measured in isolated guinea pig lumbrical muscles. Twitch height of an indirectly stimulated muscle was reduced stepwise by suitable concentrations of tubocurarine for comparison with the associated occlusion of receptors by the drug. Receptor occlusion was estimated from the effect of tubocurarine on carbachol depolarization measured extracellularly by the moving-fluid electrode technique. Roughly 75-80% of the receptor pool had to be blocked before the twitch height began to fall, and 90-95% had to be blocked before the twitch response was completely abolished. These results agree well with those found previously in vivo. Thus, the present results add further support to the earlier measurements. In particular, artifacts that might have been present because of the complex pharmacokinetic situation in vivo have been ruled out.

Animals↗
PubMed1975

A comparison of the potencies of a series of barbiturates at the neuromuscular junction and on the central nervous system.

The ability of a series of barbiturates to depress the depolarizing action of carbachol at the end-plate of guinea-pig lumbrical muscle was studied. The compounds studied were: amorbarbital, aprobarbital, barbital, barbituric acid, butabarbital, butalbital, dimethylbutylethyl barbituric acid, hexobarbital, mephobarbitak, secobarbital, thiamylal, and thiopental. The depressant activity was sensitive to small changes in structure of the compounds strongly suggesting that a specific receptor site was involved in the interaction of the drug with the tissue. The observed relative potencies on the motor end-plate were compared with their anesthetic potencies assayed on tadpoles. The two potencies went hand-in-hand for all the compounds studied, including the convulsant member of the series.

Animals↗